A phase II study of lenalidomide in patients with extranodal marginal zone B-cell lymphoma of the mucosa associated lymphoid tissue (MALT-lymphoma).

Aug 2012

Kiesewetter B, Troch M, Dolak W, Müllauer L, Lukas J, Zielinski CC, Raderer M.

Source

Austria.

Abstract

MALT lymphoma shares certain features with multiple myeloma. In view of this and the activity of lenalidomide in various B-cell lymphomas, we have initiated a phase II study of lenalidomide in patients with MALT lymphoma. Patients with histologically verified advanced MALT lymphoma were included in the study. Treatment consisted of lenalidomide 25 mg p.o. days 1-21, with a 7 day-break after each cycle. A total of 18 patients were included in the trial; 5 had gastric and 13 had extragastric MALT lymphoma, but two discontinued therapy during the first course of therapy.In the intent to treat analysis, an overall response rate of 61% was seen (11/18; 6 complete and 5 partial remissions). Three patients had stable disease, while two progressed. Side effects were manageable and included neutropenia (grade III in 3 patients) as the leading hematotoxicity. After a median follow-up of 20.3 months, one patient has died from lymphoma, while the remaining are alive and relapse-free. These data suggest activity of lenalidomide monotherapy in MALT lymphoma .

Haematologica

Analysis of Microsatellite Instability in Gastric Malt Lymphoma.

Aug 2012

Degroote A, Knippenberg L, Borght SV, Spaepen M, Matthijs G, Schaeffer DF, Owen DA, Libbrecht L, Lambein K, de Hertogh G, Tousseyn T, Sagaert X.

Abstract

Abstract In Helicobacter pylori gastritis, constant antigenic stimulation triggers a sustained B-cell proliferation. Errors made during this continuous DNA replication are supposed to be corrected by the DNA mismatch repair mechanism. Failure of this mismatch repair mechanism has been described in hereditary non-polyposis colorectal cancer (HNPCC) and results in a replication error phenotype. Inherent to their instability during replication, microsatellites are the best markers of this replication error phenotype. We aimed to evaluate the role of defects in the DNA mismatch repair mechanism and microsatellite instability (MSI) in relation to the most frequent genetic anomaly, translocation t(11;18)(q21;q21), in gastric mucosa-associated lymphoid tissue (MALT) lymphoma . Therefore, we examined 10 microsatellite loci (BAT25, BAT26, D5S346, D17S250, D2S123, TGFB, BAT40, D18S58, D17S787 and D18S69) for instability in 28 patients with MALTlymphomas. In addition, these tumors were also immunostained for MLH1, MSH2, MSH6, and PMS2, as well as screened for the presence of t(11;18)(q21;q21) by real time polymerase chain reaction (RT-PCR). We found MSI in 5/28 (18%) lymphomas, with MSI occurring in both t(11;18)(q21;q21)-positive and -negative tumors. One tumor displayed high levels of instability, and, remarkably, this was the only case displaying features of a diffuse large B-cell lymphoma. All microsatellite instable lymphomas showed a loss of MSH6 expression. In conclusion, our data suggest that a MMR-defect may be involved in the development of gastric MALT lymphomas, and that a defect of MSH6 might be associated with those MSI-driven gastric lymphomas.

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